Analysis of Tmem170 Function by RNA Silencing

Mouse Mammary Tumor Virus (MMTV) is a retrovirus that produces tumors in mice and is used as a model system for human breast cancer. After infection, a copy of the MMTV genome integrates into the host genome and enhances expression of host cellular oncogenes to produce tumors. It has recently been discovered that MMTV enhances the expression of a novel gene, Tmem170. This transmembrane protein has yet to have a specific function ascribed to it. Utilizing RNA interference, I examined the role of Tmem170 in tumor growth. I developed a series of constructs that were designed to knockdown expression of Tmem170 RNA, and transfected these constructs into a mouse mammary tumor cell line that overexpresses Tmem170. Knockdown efficiency was widely varied, but the C2 cell populations exhibited the most efficient knockdown. In cell culture, the proliferation rates of the experimental cell populations was also varied, but again, the C2 populations showed the most consistent decrease in proliferation rate. When the C2-3 population was injected into BALB/c mice in comparison with the cell population containing the empty vector, tumors were produced only from the C2-3 cells. These results indicate that Tmem170 has oncogenic potential, but further tests need to be carried out to tease out the mechanism of oncogenesis.